Identifying Antigen-Specific T and B Cells in Seronegative Rheumatoid Arthritis Synovial Tissue: Implications for Antigen-Specific Immunotherapy
Abstract
We characterized clonally-expanded T cells in blood and synovial tissue (ST) of 4 seropositive rheumatoid arthritis (RA) patients. Using simultaneous single-cell RNA and T cell receptor (TCR)alpha/Beta sequencing, we identified T cell clonotypes in paired blood and ST of newly-diagnosed, seropositive, treatment-nave HLA-DRB1*04:01+ RA patients. The transcriptomic signatures of ST-unique CD4+ TCR clonotypes highlight central memory, Th2 differentiation and IL-6 signaling. Unexpectedly, the most expanded circulating CD4+ and CD8+ clonotypes display cytotoxic polyfunctional proinflammatory capacity. Among these, TCR sequencing and tetramer staining identified EBV- and CMV-specific clonotypes, some of which migrated to ST, lodging adjacent to blood vessels and dendritic cells. Our findings implicate antigen-specific Th2 and central memory CD4 T cells and cytotoxic viral-specific bystander T cell clones in early RA synovial inflammation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2021
- Accession Number
- AD1134776
Entities
People
- Ranjeny Thomas
Organizations
- University of Queensland